First-onset Major Depressive Disorder Research Articles

Relationship Between Affective Temperaments and Suicide Risk in Patients With First-Onset Major Depressive Disorder.

BackgroundPeople may endorse suicidal behavior during a major depressive episode. Affective temperaments may play a role in this risk. We explored the relationship between affective temperaments and suicide and identified some traits that can predict suicide risk in depression.Materials and MethodsWe analyzed the results of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A) in 284 participants recruited from a psychiatric clinic and the community in Beijing and compared the subscale scores (temperaments of cyclothymic, dysthymic, anxious, irritable, and hyperthymic) among major depressive disorders (MDDs) vs. the general population as well as depressive patients with vs. without suicide risk, using Student’s test, chi-square test, rank-sum test, and multivariable regression modeling.ResultsThe incidence of suicidal risk in depressive subjects was 47.62% (80/168). Being unmarried (p < 0.001), unemployed (p = 0.007), and temperaments of dysthymic, cyclothymic, anxious, and irritable scores (all p < 0.001) were significantly more prevalent in patients with depression than in the general population. Young age (p < 0.001), female sex (p = 0.037), unmarried (p = 0.001), more severe depression (p < 0.001), and dysthymic, anxious, and cyclothymic temperament (all p < 0.05) were significantly more prevalent in patients with depressive disorder than those without suicide risk. The logistic regression analysis showed that younger age (odds ratio [OR] = 0.937, 95% CI 0.905∼0.970), female sex (OR = 2.606, 95% CI 1.142∼5.948), more severe depression (OR = 1.145, 95% CI 1.063∼1.234), cyclothymic temperament (OR = 1.275, 95% CI 1.102∼1.475), and dysthymic temperament (OR = 1.265, 95% CI 1.037∼1.542) were all independently associated with high suicidal risk in patients with first-onset major depression (p < 0.05).ConclusionTemperament traits differ between the general population and people suffering from MDD. Subjects with MDD who have much more severe depressive symptoms and a cyclothymic or dysthymic temperament were at a high risk of suicide.

The impact of self-efficacy on first onset and prognosis of major depressive disorder: findings from a longitudinal study in a sample of Chinese first-year university students.

Self-efficacy is a pivotal factor in the etiology and prognosis of major depression. However, longitudinal studies on the relationship between self-efficacy and major depressive disorder (MDD) are scarce. The objectives were to investigate: (1) the associations between self-efficacy and the 1-year and 2-year risks of first onset of MDD and (2) the associations between self-efficacy and the 1-year and 2-year risks of the persistence/recurrence of MDD, in a sample of first-year university students. We followed 8079 first-year university students for 2 years from April 2018 to October 2020. MDD was ascertained by the Chinese version of the Composite International Diagnostic Interview (CIDI-3.0) based on self-report. Self-efficacy was measured by the 10-item General Self-efficacy (GSE) scale. Random effect logistic regression modeling was used to estimate the associations. Among participants without a lifetime MDD, the data showed that participants with high baseline GSE scores were associated with a higher risk of first onset of MDD over 2 years [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.08]. Among those with a lifetime MDD, participants with high baseline GSE scores were less likely to have had a MDD over 2 years (OR 0.93, 95% CI 0.88-0.99) compared to others. A high level of GSE may be protective of the risk of persistent or recurrent MDD. More longitudinal studies in university students are needed to further investigate the impact of GSE on the first onset of MDD.

Relationship between initial self-perceived depressive symptoms and disease severity in working patients with first-onset major depressive disorder.

The severity of major depressive disorder (MDD), which is related to the depressive symptoms, is a predictor of clinical outcomes and may be used to determine the appropriate treatment. However, there is a lack of systematic research on the relationship between early depressive symptoms and MDD severity. This study aimed to clarify the association between initial depressive symptoms and MDD severity in working patients. We assessed 118 patients aged over 20 years who visited the Neuropsychiatry Department of the Osaka City University Hospital following their first episode of MDD. Logistic regression analyses were performed to estimate the odds ratios (OR) with 95% confidence intervals (CI) for the associations between age, gender, marital status, working hours, and initial self-perceived depressive symptoms and MDD severity. Age and working hours were analyzed as continuous variables, and gender (man, woman), marital status (married, single) and severity (mild to moderate MDD, severe to very severe MDD) were analyzed as categorical variables. The most common initial self-perceived symptom was "depressed mood," followed by "fatigue or loss of energy nearly every day." The univariate analysis found no association between age, gender, marital status, or working hours and MDD severity. Initial self-perceived non-somatic symptoms were associated with increased odds of having severe MDD (odds ratio = 3.32, 95% confidence interval 1.46-7.58), and this association persisted in the adjusted model (odds ratio = 3.35, 95% confidence interval 1.47-7.60). Initial self-perceived non-somatic depressive symptoms are significantly associated with MDD severity at its first onset. Workplace support may lead to the early detection and treatment of working patients with non-somatic symptoms.

Psychological factors for the onset of depression: a meta-analysis of prospective studies

ObjectivesA comprehensive overview of the evidence for factors derived from leading psychological theories of the onset of major depressive disorder (MDD) that underpin psychological interventions is scarce . We aimed...

Abnormal functional connectivity of habenula in untreated patients with first-episode major depressive disorder

Major depressive disorder (MDD) is associated with abnormalities in emotional/cognitive processing and low reward sensitivity. The habenula has a pivotal role in these processes that may contribute to depression. However, there has been little research on the abnormal connectivity between the habenula and whole brain of first-onset MDD. We aimed to explore the differences of functional connectivity between patients and healthy controls using functional magnetic resonance imaging. We used seed-based resting-state fMRI to examine functional connectivity between the habenula and whole-brain in 49 first-episode depressive patients and 25 healthy controls. Compared to controls, patients with MDD demonstrated significant increases in functional connectivity between the habenula and the dorsolateral prefrontal cortex (dlPFC). Furthermore, the receiver operating characteristic (ROC) curve proved that connectivity between the habenula and dlPFC was highly predictive. Additionally, there was a positive correlation between Hamilton Rating Scale for Depression (HAMD) score and functional connectivity between the habenula and right dlPFC. We found that the aberrant functional connectivity to the habenula and dlPFC can distinguish MDD patients from the normal.

DNA methylation of HPA-axis genes and the onset of major depressive disorder in adolescent girls: a prospective analysis

The stress response system is disrupted in individuals with major depressive disorder (MDD) as well as in those at elevated risk for developing MDD. We examined whether DNA methylation (DNAm) levels of CpG sites within HPA-axis genes predict the onset of MDD. Seventy-seven girls, approximately half (n = 37) of whom were at familial risk for MDD, were followed longitudinally. Saliva samples were taken in adolescence (M age = 13.06 years [SD = 1.52]) when participants had no current or past MDD diagnosis. Diagnostic interviews were administered approximately every 18 months until the first onset of MDD or early adulthood (M age of last follow-up = 19.23 years [SD = 2.69]). We quantified DNAm in saliva samples using the Illumina EPIC chip and examined CpG sites within six key HPA-axis genes (NR3C1, NR3C2, CRH, CRHR1, CRHR2, FKBP5) alongside 59 genotypes for tagging SNPs capturing cis genetic variability. DNAm levels within CpG sites in NR3C1, CRH, CRHR1, and CRHR2 were associated with risk for MDD across adolescence and young adulthood. To rule out the possibility that findings were merely due to the contribution of genetic variability, we re-analyzed the data controlling for cis genetic variation within these candidate genes. Importantly, methylation levels in these CpG sites continued to significantly predict the onset of MDD, suggesting that variation in the epigenome, independent of proximal genetic variants, prospectively predicts the onset of MDD. These findings suggest that variation in the HPA axis at the level of the methylome may predict the development of MDD.

The role of familial risk, parental psychopathology, and stress for first-onset depression during adolescence

BackgroundAdolescence represents a critical developmental period during which the initial onset of depression emerges. Family risk for depression is a salient risk factor for the initial onset of Major Depressive Disorder (MDD). We examined the effects of familial risk, stress, and behavior on the risk of developing first-onset depression. MethodsAdolescents aged 12 to 15 with high (n = 166) or low (n = 159) familial risk for depression were assessed annually for up to five years. Stress was assessed using the Stressful Life Events Schedule and Childhood Trauma Questionnaire. The Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version was administered to the adolescents and their parents to assess lifetime psychiatric conditions and diagnose MDD onset. Survival and path analyses were used in tandem to determine the risk for first-onset depression as well as the contributions of additional direct and indirect pathways to onset. ResultsHigh-risk adolescents were eight times more likely to develop first-onset depression compared with low-risk adolescents. The path analyses revealed that the presence of maternal behavioral disorders and increased recent life stress directly predicted an initial onset of MDD in high-risk adolescents. LimitationsThe small samples used in this study limit the generalizability of these findings. ConclusionsAdolescents at high familial risk for depression had an increased risk for the emergence of first-onset depression during adolescence. Stress and maternal behavioral psychopathology directly contributed to depression onset independently of familial risk, while childhood trauma exerted an indirect effect on first-onset MDD through recent stress.

The Association Between the Sedative Loads and Clinical Severity Indicators in the First-Onset Major Depressive Disorder.

Background: High sedative use in a major depressive episode may imply specific clinical features. This study aims to examine the correlation between sedative use and clinical severity indicators in the initial treatment phase of first-onset major depressive disorder.Methods: A study cohort in the first episode of major depressive disorder was used to conduct pharmacological dissection. All participants had at least a 2-year follow-up period with a complete treatment record. The defined daily dose of antidepressants and augmentation agents were calculated as the antidepressant load and augmentation load, respectively. Sedative use, which was calculated as the equivalent dosage of lorazepam, were defined as the sedative load. These psychotropic loads were measured monthly and the averaged psychotropic loads for each day were obtained.Results: A total of 106 individuals (75.5% female) were included. The mean duration of disease course in participants was 5.5 ± 3.5 years. In the multiple regression analysis, after controlling for other classes of psychotropics and comorbid anxiety disorders, the sedative load independently correlated with higher number of antidepressants used, higher number of antidepressant used with an adequate dose and duration, more psychiatric emergency and outpatient visits within 2 years of disease onset.Conclusion: High loading of sedatives correlated with several indicators of clinical severity in major depressive disorder. The sedative load may be used as a specifier to identify subgroups in patients with major depressive disorder.

A longitudinal study of neurotrophic, oxidative, and inflammatory markers in first-onset depression in midlife women.

Prospective studies have shown during the years preceding and following menopause, also known as "menopause transition", that midlife women are at higher risk for developing first-onset major depressive disorder (MDD). The biological factors associated with risk and resilience in this population are, however, largely unknown. Considering the growing body of evidence suggesting that inflammation, oxidative stress, and brain-derived neurotrophic factor (BDNF) are associated with the pathophysiology of MDD, we investigated serum levels of protein carbonyl, lipid peroxidation (thiobarbituric acid reactive substances-TBARS), thiol group content, BDNF, 3-nitrotyrosine, and heat shock protein 70 (HSP70) in a longitudinal cohort of first-onset MDD. One hundred and forty-eight women from the Harvard Study of Moods and Cycles, a prospective study of midlife women monitored throughout the transition to menopause, were studied. Within- and between-groups analyses of these peripheral markers were conducted in 37 women who developed and 111 women that did not develop MDD during the 3-year follow-up period. In women who developed MDD, HSP70 and 3-nitrotyrosine were elevated at baseline, whereas TBARS were elevated 6months prior to development of MDD, as compared to those who did not develop MDD. Within-group analyses showed that HSP70, 3-nitrotyrosine, and BDNF decreased over time, whereas protein carbonyl was elevated only at 12months prior to development of MDD. In women who did not develop MDD, HSP70 and thiol decreased over time. The development of MDD in midlife women may be associated with a systemic cascade of pro-oxidative and pro-inflammatory events including increased HSP70, 3-nitrotyrosine, protein carbonyl, and lipid peroxidation and decreased BDNF.

Association between serotonin transporter genotype, brain structure and adolescent-onset major depressive disorder: a longitudinal prospective study.

The extent to which brain structural abnormalities might serve as neurobiological endophenotypes that mediate the link between the variation in the promoter of the serotonin transporter gene (5-HTTLPR) and depression is currently unknown. We therefore investigated whether variation in hippocampus, amygdala, orbitofrontal cortex (OFC) and anterior cingulate cortex volumes at age 12 years mediated a putative association between 5-HTTLPR genotype and first onset of major depressive disorder (MDD) between age 13–19 years, in a longitudinal study of 174 adolescents (48% males). Increasing copies of S-alleles were found to predict smaller left hippocampal volume, which in turn was associated with increased risk of experiencing a first onset of MDD. Increasing copies of S-alleles also predicted both smaller left and right medial OFC volumes, although neither left nor right medial OFC volumes were prospectively associated with a first episode of MDD during adolescence. The findings therefore suggest that structural abnormalities in the left hippocampus may be present prior to the onset of depression during adolescence and may be partly responsible for an indirect association between 5-HTTLPR genotype and depressive illness. 5-HTTLPR genotype may also impact upon other regions of the brain, such as the OFC, but structural differences in these regions in early adolescence may not necessarily alter the risk for onset of depression during later adolescence.

Predictors of first lifetime onset of major depressive disorder in young adulthood.

The first onset of major depressive disorder (MDD) most frequently occurs in young adulthood. However, few studies have examined predictors of first lifetime MDD during this high-risk period. The present study examined a broad range of demographic, clinical, and psychosocial variables as prospective predictors of first onset of MDD in a large community sample of young adults (N = 502) from the Oregon Adolescent Depression Project. Between ages 19-31, 35.3% of the sample had a first lifetime MDD episode. Female gender, familial loading of mood disorders, history of childhood sexual abuse, prior history of anxiety disorder, poor self-reported physical health, and subthreshold depressive symptoms significantly predicted MDD onset. In a multivariate model, female gender, familial loading of mood disorders, and subthreshold depression each contributed unique variance in predicting first lifetime MDD. This model had a moderate-to-large effect in predicting MDD onset. Gender did not moderate the other predictors, and the magnitude of the effects did not diminish over the course of the follow-up. These findings indicate that a number of risk factors significantly predict first lifetime MDD in young adulthood, and that simple multivariate risk models may be useful for identifying individuals at high risk for MDD.

Associations of current and remitted major depressive disorder with brain atrophy: the AGES–Reykjavik Study

To examine whether lifetime DSM-IV diagnosis of major depressive disorder (MDD), including age at onset and number of episodes, is associated with brain atrophy in older persons without dementia. Within the population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 4354 persons (mean age 76 ± 5 years, 58% women) without dementia had a 1.5-T brain magnetic resonance imaging (MRI) scan. Automated brain segmentation total and regional brain volumes were calculated. History of MDD, including age at onset and number of episodes, and MDD in the past 2 weeks was diagnosed according to DSM-IV criteria using the Mini-International Neuropsychiatric Interview (MINI). Of the total sample, 4.5% reported a lifetime history of MDD; 1.5% had a current diagnosis of MDD (including 75% with a prior history of depression) and 3.0% had a past but no current diagnosis (remission). After adjusting for multiple covariates, compared to participants never depressed, those with current MDD (irrespective of past) had more global brain atrophy [B = -1.25%, 95% confidence interval (CI) -2.05 to -0.44], including more gray- and white-matter atrophy in most lobes, and also more atrophy of the hippocampus and thalamus. Participants with current, first-onset MDD also had more brain atrophy (B = -1.62%, 95% CI -3.30 to 0.05) whereas those remitted did not (B = 0.06%, 95% CI -0.54 to 0.66). In older persons without dementia, current MDD, irrespective of prior history, but not remitted MDD was associated with widespread gray- and white-matter brain atrophy. Prospective studies should examine whether MDD is a consequence of, or contributes to, brain volume loss and development of dementia.

Relation between locus of control and parental rearing patterns of adolescent with major depressive disorder

Objective To explore the locus of control and the relationship with parenting patterns of ado-lescents with first-onset major depressive disorder (MDD). Methods Patients with first-onset MDD (n= 98) and controls (n=98) were investigated by Sphere of Control Questionaire and EMBU, the results were compared and analyzed correlatively. Results The scores of the individual strength scale ( 37.47±13.66) and the relations with people scale ( 38.65±13.19 ) of patients were significantly lower(P 0.05)than the controls' (39.12±9.50). The scores of patients' paternal excessive inter-ference factor(2.66±0.49) , maternal excessive protection/interference (2.79±0.55 ) and rejection/denial fac-tor(2.55±0.39) of EMBU were significantly higher(P<0.05)than controls' [(2.17±0.58),(2.17±0.49) and( 1.75±0.51 ) each]. The scores of patients' paternal affection/understanding factor were significantly posi-tively correlative with patients' scores of relations with people (r=0.27, P<0.05), maternal affection/under-standing factor was significantly positively correlative with patients' scores of individual strength (r=0.21, P <0.05) and relations with people(r=0.23, P<0.05 ) , while maternal excessive interference/excessive protection and individual strength (r=-0.24, P<0.05 ) and relations with people (r=-0.22, P<0.05), maternal rejec-tion/denial and individual strength (r=-0.26, P<0.05) were significantly negatively correlative. Conclusion Adolescents with MDD have abnormal locus of control,which might be correlative with their parenting patterns. Key words: Adolescent; MDD; Locus of control; Parenting pattern

Lifetime comorbidities between phobic disorders and major depression in Japan: results from the World Mental Health Japan 2002–2004 Survey

Although often considered of minor significance in themselves, evidence exists that early-onset phobic disorders might be predictors of later more serious disorders, such as major depressive disorder (MDD). The purpose of this study is to investigate the association of phobic disorders with the onset of MDD in the community in Japan. Data from the World Mental Health Japan 2002-2004 Survey were analyzed. A total of 2,436 community residents aged 20 and older were interviewed using the WHO Composite International Diagnostic Interview 3.0 (response rate, 58.4%). A Cox proportional hazard model was used to predict the onset of MDD as a function of prior history of DSM-IV specific phobia, agoraphobia, or social phobia, adjusting for gender, birth-cohort, other anxiety disorders, education, and marital status at survey. Social phobia was strongly associated with the subsequent onset of MDD (hazard ratio [HR]=4.1 [95% CI: 2.0-8.7]) after adjusting for sex, birth cohort, and the number of other anxiety disorders. The association between agoraphobia or specific phobia and MDD was not statistically significant after adjusting for these variables. Social phobia is a powerful predictor of the subsequent first onset of MDD in Japan. Although this finding argues against a simple neurobiological model and in favor of a model in which the cultural meanings of phobia play a part in promoting MDD, an elucidation of causal pathways will require more fine-grained comparative research.

COMPARISON OF THE POLYMORPHISMS OF ANDROGEN RECEPTOR GENE AND ESTROGEN α AND β GENE BETWEEN ADOLESCENT FEMALES WITH FIRST-ONSET MAJOR DEPRESSIVE DISORDER AND CONTROLS

This study was to elucidate the role of genetic variation in androgen receptor (AR) gene, estrogen receptor α (ER α) and ER β gene on first-onset major depressive disorder (MDD) in female adolescents. Results showed that AR gene in MDD group have shorter microsatellites’ length, and ER β gene have shorter microsatellites’ length and higher rates of S alleles, SS, genotype, and lower rate of LL genotype than control group. The results suggest that shorter length of AR and ER β gene microsatellites might influence the onset of MDD in female adolescents, a further elucidation of the mechanisms is warranted.

Comorbid psychiatric disorders in depressed outpatients: Demographic and clinical features

Background This study evaluated the clinical and sociodemographic features associated with various degrees of concurrent comorbidity in adult outpatients with nonpsychotic major depressive disorder (MDD). Methods Outpatients enrolled in the STAR*D trial completed the Psychiatric Diagnostic Screening Questionnaire (PDSQ). An a priori 90% specificity threshold was set for PDSQ responses to ascertain the presence of 11 different concurrent DSM-IV Axis I disorders. Results Of 1376 outpatients, 38.2% had no concurrent comorbidities, while 25.6% suffered one, 16.1% suffered two, and 20.2% suffered three or more comorbid conditions. Altogether, 29.3% met threshold for social anxiety disorder, 20.8% for generalized anxiety disorder, 18.8% for posttraumatic stress disorder, 12.4% for bulimia, 11.9% for alcohol abuse/dependence, 13.4% for obsessive–compulsive disorder, 11.1% for panic disorder, 9.4% for agoraphobia, 7.3% for drug abuse/dependence, 3.7% for hypochondriasis, and 2.2% for somatoform disorder. Those with more concurrent Axis I conditions had earlier ages at first onset of MDD, longer histories of MDD, greater depressive symptom severity, more general medical comorbidity (even though they were younger than those with fewer comorbid conditions), poorer physical and mental function, health perceptions, and life satisfaction; and were more likely to be seen in primary care settings. Limitations Participants had to meet entry criteria for STAR*D. Ascertainment of comorbid conditions was not based on a structured interview. Conclusions Concurrent Axis I conditions (most often anxiety disorders) are very common with MDD. Greater numbers of concurrent comorbid conditions were associated with increased severity, morbidity, and chronicity of their MDD.

First Episode of Depression in Children at Low and High Familial Risk for Depression

To examine the development of first-onset major depressive disorder (MDD) in children at high and low familial risk for depression in a prospective study. High-risk children (n = 76) who were free of any lifetime affective disorder and had at least one first-degree and one second-degree relative with a lifetime history of childhood-onset, recurrent, bipolar, or psychotic depression were included. Low-risk children (n = 63) were included if they were free of any lifetime psychiatric disorder and had no first-degree relatives and fewer than 20% of their second-degree relatives with a lifetime affective disorder. Children and their parents were assessed in a prospective design using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic version (K-SADS-E). The average interval between follow-up interviews was 18 months, and the average follow-up period was 6 years. High-risk children had approximately a threefold increased risk of developing first-onset MDD compared with low-risk children (odds ratio = 3.21). The average age of new-onset MDD was 14.0 +/- 2.9 years (range 9.5-19.5 years). Above and beyond the familial loading for MDD, mother's lifetime anxiety disorder (odds ratio = 2.84) and lifetime behavioral disorder (odds ratio = 3.25) in the child significantly added to the risk of developing a first-onset MDD. Having high familial loading for affective disorders, a mother with and anxiety disorder, and a behavioral disorder in the child all significantly contributed to the risk of developing depression.

Social and physical health risk factors for first-onset major depressive disorder in a community sample.

Using prospective data on 3,170 respondents aged 18 years and over who were at risk for a first-onset major depression from the New Haven site of the Epidemiologic Catchment Area (ECA) study, these analyses assessed the effects of social status, physical health status, and social isolation on first-onset depression in a 1-year period, controlling for demographic characteristics and baseline psychiatric factors. Among the assessed potential risk factors, poverty status [odds ratio (OR = 2.034, P < 0.05)] and confinement to a bed or chair (OR = 4.015, P < 0.05) were independently associated with an increased risk for a first-onset depressive episode when controlling for gender, age, past history of substance abuse, and subclinical depressive symptoms. The effects of poverty, and to a lesser degree homebound status, were substantially reduced when controlling for degree of isolation from friends and family, suggesting that social isolation mediates some of the relationships between social and physical statuses and major depression.